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Interim STOP 2G-TKI results support TFR from dasatinib, nilotinib


Blood, January 2017; advance online publication

: Preliminary findings from the STOP 2G-TKI study suggest that carefully selected chronic myeloid leukemia (CML) patients using dasatinib or nilotinib can achieve treatment-free remission (TFR).

The trial’s interim analysis reports data for 60 patients who discontinued dasatinib or nilotinib after a median of at least 3 years’ treatment and had a deep, undetectable molecular response (MR4.5; BCR–ABL1 ≤0.0032%) for at least 2 years. The patients were followed up for a median of 47 months after discontinuation.

The patients were discontinuing first-line treatment in 13.3% of cases, second-line treatment in 66.7% of cases and third-line therapy in 20.0%, report Delphine Rea, from Hôpital Saint-Louis in Paris, France, and co-authors in Blood.

Molecular relapse occurred in 43.3% of patients after a median of 4 months. The cumulative incidence of molecular relapse was 35.00% at 12 months and 44.76% at 48 months, with estimated TFRs of 63.33% and 53.57% at these timepoints, respectively.

Of the 26 patients who relapsed, 25 returned to treatment within a median of 1.1 months, with all but two patients returning to their last tyrosine kinase inhibitor (TKI). One patient delayed restarting nilotinib for 5.8 months because of cardiovascular concerns and chose to use bosutinib, and a second switched from nilotinib to dasatinib because of tolerance issues.

Seven patients who had relapsed during TFR had a second attempt at discontinuation after a median of 31 months of therapy, but five lost their major molecular response (MMR; BCR–ABL1 ≤0.1%) status again within 3 months, the authors note.

Landmark analysis conducted 3 months after discontinuation in the 49 patients without loss of molecular response at this time showed that 38 patients had maintained MR4.5, including 31 who had an undetectable level, and 11 had a BCR–ABL1 level above MR4.5 but still within an MMR. At 48 months, the cumulative incidence of molecular relapse was 17.59% and 81.82% in these groups, respectively, with corresponding TFR rates at this time of 79.78% and 18.18%.

Patients were also significantly less likely to experience molecular relapse if they had been prescribed first-line dasatinib or nilotinib or if they had previously had an optimal response to imatinib than if they previously showed a suboptimal response or resistance to imatinib, with 48-month rates of 35.51% versus 76.92%. And the 48-month TFR rates in the two groups were 62.36% and 23.08%, respectively.

But molecular relapse was not predicted by Sokal score, age, gender, prior use of interferon-alpha, duration of TKI therapy or duration of undetectable MR4.5.

“Here, we demonstrate that TFR is not restricted to imatinib-treated patients and that 1st or subsequent line dasatinib or nilotinib may also be successfully and safely stopped,” Rea et al summarise.

While noting that there were no safety issues in the trial and that all patients with a molecular relapse regained MMR and a deep molecular response, they caution that “the rapid increase in BCR-ABL1 transcripts during the time-window between MMR loss and treatment resumption highlights the necessity of a prompt treatment reintroduction once a molecular relapse is identified, as we cannot exclude that a long delay may expose to the accumulation of additional genetic events and the loss of disease control.”


By Lynda Williams, Senior medwireNews reporter

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